The human immunodeficiency virus type 1 (HIV-1) has been defined as the etiologic agent of he acquired immune deficiency syndrome (AIDS). Although intensive research has been directed toward management of this lethal disease, to date no facile means of prevention and treatment has been identified. Recently, human saliva was found to inhibit the infectivity of HIV-1 into human peripheral blood lymphocytes, suggesting that saliva and possibly other secretory fluids contain human-derived products having anti- HIV-1 activity. The objective of the proposed study is to isolate and identify the inhibitory factors in human secretory fluids and to then study the modes of action of these factors, with the ultimate goal of developing therapeutic interventions against HIV-1 infection. Preliminary results indicate that perchloric acid-stable factors(s) in human whole saliva inhibit the infectivity of HIV-1, as judged by the inhibition of expression of reverse transcriptase activity released into the extracellular milieu of HIV-1 infected CEM cells. Proposed studies will include screening of various secretory fluids (milk, tears, whole saliva, parotid saliva, and submandibular/sublingual saliva) and of a number of purified secretory components (lactoferrin, IgA, lactoferrin-IgA complexes, lysozyme, peroxidase, agglutinins and secretory leukocyte protease inhibitor) for anti-HIV-1 activity. Concomitantly, native secretory fluids will be fractionated by a number of currently used chromatographic procedures, with the exact sequence of procedures dependent upon the fractionation patterns of the anti-HIV-1 activities. Further characterization of the anti-HIV-1 activities will include determination of the specificities of the activities toward different virus isolates and different target cells, and determination if the factors can prevent syncytia formation by HIV-1- infected cells. Together, these studies should provide valuable information regarding the nature of human-derived weapons against HIV-1 and may lead to effective therapeutic intervention of HIV-1 infections.